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The Cochrane Database of Systematic... Aug 2021Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be beneficial for people with chronic liver... (Review)
Review
BACKGROUND
Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be beneficial for people with chronic liver diseases.
OBJECTIVES
To assess the beneficial and harmful effects of vitamin D supplementation in adults with chronic liver diseases.
SEARCH METHODS
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and enquired experts and pharmaceutical companies as to additional trials. All searches were up to November 2020.
SELECTION CRITERIA
Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D (cholecalciferol) or vitamin D (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included 27 randomised clinical trials with 1979 adult participants. This review update added 12 trials with 945 participants. We assessed all trials as at high risk of bias. All trials had a parallel-group design. Eleven trials were conducted in high-income countries and 16 trials in middle-income countries. Ten trials included participants with chronic hepatitis C, five trials participants with liver cirrhosis, 11 trials participants with non-alcoholic fatty liver disease, and one trial liver transplant recipients. All of the included trials reported the baseline vitamin D status of participants. Participants in nine trials had baseline serum 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), whilst participants in the remaining 18 trials were vitamin D insufficient (less than 20 ng/mL). Twenty-four trials administered vitamin D orally, two trials intramuscularly, and one trial intramuscularly and orally. In all 27 trials, the mean duration of vitamin D supplementation was 6 months, and the mean follow-up of participants from randomisation was 7 months. Twenty trials (1592 participants; 44% women; mean age 48 years) tested vitamin D (cholecalciferol); three trials (156 participants; 28% women; mean age 54 years) tested vitamin D; four trials (291 participants; 60% women; mean age 52 years) tested 1,25-dihydroxyvitamin D; and one trial (18 participants; 0% women; mean age 52 years) tested 25-hydroxyvitamin D. One trial did not report the form of vitamin D. Twelve trials used a placebo, whilst the other 15 trials used no intervention in the control group. Fourteen trials appeared to be free of vested interest. Eleven trials did not provide any information on clinical trial support or sponsorship. Two trials were funded by industry. We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on all-cause mortality (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.51 to 1.45; 27 trials; 1979 participants). The mean follow-up was 7 months (range 1 to 18 months). We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) (follow-up: 12 months); serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants); myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants); thyroiditis (RR 0.33, 95% CI 0.01 to 7.91; 1 trial; 68 participants); circular haemorrhoidal prolapse (RR 3.00, 95% CI 0.14 to 65.9; 1 trial; 20 participants); bronchopneumonia (RR 0.33, 95% CI 0.02 to 7.32; 1 trial 20 participants); and non-serious adverse events. The certainty of evidence for all outcomes is very low. We found no data on liver-related morbidity such as gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, ascites, or liver cancer. There were also no data on health-related quality of life. The evidence is also very uncertain regarding the effect of vitamin D versus placebo or no intervention on rapid, early, and sustained virological response in people with chronic hepatitis C.
AUTHORS' CONCLUSIONS
Given the high risk of bias and insufficient power of the included trials and the very low certainty of the available evidence, vitamin D supplementation versus placebo or no intervention may increase or reduce all-cause mortality, liver-related mortality, serious adverse events, or non-serious adverse events in adults with chronic liver diseases. There is a lack of data on liver-related morbidity and health-related quality of life. Further evidence on clinically important outcomes analysed in this review is needed.
Topics: Adult; Dietary Supplements; Female; Hepatitis C, Chronic; Humans; Male; Middle Aged; Quality of Life; Vitamin D
PubMed: 34431511
DOI: 10.1002/14651858.CD011564.pub3 -
Cureus May 2021Renal and hepatic functions are often mingled through both the existence of associated primary organ diseases and hemodynamic co-relationship. The primary objective of... (Review)
Review
Renal and hepatic functions are often mingled through both the existence of associated primary organ diseases and hemodynamic co-relationship. The primary objective of this study was to sum up the relationship between autoimmune hepatitis (AIH) on renal tubular acidosis (RTA) and the stages of the disease. A systematic review was performed for 24 trials. A total of 3687 patients were included. The incidence of RTA occurring and short-term mortality reduction was seen in two groups; for an overall effect: Z = 2.85 (P = 0.004) a total 95% CI of 0.53 [0.34, 0.82]. Only one patient with alcoholic liver cirrhosis was found to have an incomplete type of RTA. Test for overall effect: Z = 2.28 (P = 0.02) 95% CI of 2.83 [1.16, 6.95]. A reduction in fatal infections with dual therapy of corticosteroid plus N-acetylcysteine (NAC) test for overall effect: Z = 3.07 (P = 0.002) with 95% CI of 0.45 [0.27, 0.75]. Autoimmune diseases are the most frequent underlying cause of secondary RTA in adults. The primary renal disease must be actively excluded in all patients with hepatic failure by aggressive clinical and laboratory evaluations.
PubMed: 34079685
DOI: 10.7759/cureus.15287 -
JHEP Reports : Innovation in Hepatology Oct 2020Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this...
BACKGROUND & AIMS
Granulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this study was to synthesise available evidence on the efficacy of G-CSF in AH.
METHODS
This is a meta-analysis of randomised controlled trials evaluating the risk of death at 90 days and the risk of infection.
RESULTS
Seven studies were included. Of a total of 396 patients, 336 had AH, 197 patients were treated with G-CSF, and 199 received placebo or pentoxifylline. In overall meta-analysis, G-CSF therapy was associated with a reduced risk of death at 90 days (odds ratio [OR] 0.28; 95% CI 0.09-0.88; = 0.03). There was high heterogeneity between studies ( <0.001; = 80%). Five studies were performed in Asia and 2 in Europe. In the subgroup analysis of studies performed in Asia, G-CSF was associated with a reduced risk of death (OR 0.15; 95% CI 0.08-0.28; <0.001; heterogeneity: = 0.5, = 0%). In European studies, G-CSF tended to increase mortality compared with controls, although the difference was not significant (OR 1.89; 95% CI 0.90-3.98; = 0.09; heterogeneity: = 0.8, = 0%). In Asian studies, occurrence of infection was less frequent in G-CSF patients than in controls (OR 0.12; 95% CI 0.06-0.23; <0.001; heterogeneity: = 0.7, = 0%), whilst in European studies, this occurrence was not statistically different (OR 0.92; 95% CI 0.50-1.68; = 0.78; heterogeneity: = 0.5, = 0%). In sensitivity analyses, excluding studies that included patients with acute-on-chronic liver failure (ACLF) other than AH, patients with less severe AH, or patients with non-response to corticosteroids, results were similar to those of overall analyses, both for mortality and occurrence of infection.
CONCLUSIONS
Granulocyte colony-stimulating factor therapy may improve the prognosis of patients with severe AH. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.
LAY SUMMARY
The main finding of this meta-analysis is that the use of granulocyte colony-stimulating factor (G-CSF) is associated with a mortality reduction of more than 70% at 3 months amongst patients with alcoholic hepatitis (AH) compared with controls who did not receive this therapy. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for patients with AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.
PubMed: 32775975
DOI: 10.1016/j.jhepr.2020.100139 -
Cells Feb 2023Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups a spectrum of conditions varying from simple... (Review)
Review
Diabetic and obese patients have a high prevalence of non-alcoholic fatty liver disease (NAFLD). This condition groups a spectrum of conditions varying from simple steatosis to non-alcoholic steatohepatitis (NASH), with or without fibrosis. Multiple factors are involved in the development of NAFLD. However, details about its pathogenesis and factors that promote the progression to NASH are still missing. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) regulate metabolic, immune, and hepatic stellate cell functions. Increasing evidence suggests they may have roles in the progression from NAFLD to NASH. Following the PRISMA reporting guidelines, we conducted a systematic review to evaluate all clinical and experimental studies published in the literature correlating GH and IGF-1 to inflammation and fibrosis in NAFLD and NASH. Our results showed that GH and IGF-1 have a fundamental role in the pathogenesis of NASH, acting in slightly different ways to produce a synergic effect. Indeed, GH may mediate its protective effect in the pathogenesis of NASH by regulating lipogenesis pathways, while IGF-1 has the same effect by regulating cholesterol transport. Therefore, they could be used as therapeutic strategies in preventing NAFLD progression to NASH.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Growth Hormone; Insulin-Like Growth Factor I; Insulin; Liver Cirrhosis; Human Growth Hormone; Insulin, Regular, Human; Hepatitis
PubMed: 36831184
DOI: 10.3390/cells12040517 -
Diabetes/metabolism Research and Reviews Sep 2019An association between diabetes mellitus (DM) and liver cirrhosis is well-known, but estimates of the prevalence of DM in patients with liver cirrhosis vary widely. A... (Review)
Review Meta-Analysis
An association between diabetes mellitus (DM) and liver cirrhosis is well-known, but estimates of the prevalence of DM in patients with liver cirrhosis vary widely. A systematic review was undertaken to determine the prevalence of DM in adult patients with liver cirrhosis. The Medline, EMBASE, and Cochrane Library databases were searched for peer-reviewed studies published in English (1979-2017) that investigated the prevalence of diabetes in adult patients with cirrhosis. Pooled estimates of prevalence of DM were determined for all eligible patients and according to aetiology and severity of liver disease. Fifty-eight studies satisfied criteria for inclusion, with 9705 patients included in the pooled prevalence analysis. The overall prevalence of DM was 31%. The prevalence of DM was highest in patients with nonalcoholic fatty liver disease (56%), cryptogenic (51%), hepatitis C (32%), or alcoholic (27%) cirrhosis. For assessing prevalence of DM as a function of severity of liver disease, evaluable data were available only for hepatitis C and hepatitis B cirrhosis. DM may be more prevalent in cirrhosis than previously thought. This has implications for prognosis and treatment in these patients.
Topics: Diabetes Mellitus; Humans; Liver Cirrhosis; Prevalence; Prognosis; Risk Factors
PubMed: 30901133
DOI: 10.1002/dmrr.3157 -
Clinical Kidney Journal Apr 2022Patients receiving dialysis for end-stage kidney disease (ESKD) commonly co-exhibit risk factors for hepatic impairment. This systematic review and meta-analysis aimed...
BACKGROUND
Patients receiving dialysis for end-stage kidney disease (ESKD) commonly co-exhibit risk factors for hepatic impairment. This systematic review and meta-analysis aimed to quantify the coexistence of chronic liver disease (CLD) and characterize risk factors and outcomes.
METHODS
We searched the following databases from inception to May 2021: CINAHL, Cochrane Library, Embase, Kings Fund Library, MEDLINE and PubMed. The protocol was pre-registered on PROSPERO (study ID: CRD42020206486). Studies were assessed against three inclusion criteria: adults (>18 years) with ESKD receiving dialysis, primary outcome involving CLD prevalence and publications in English. Moderator analysis was performed for age, gender, study size and publication year. Sensitivity analysis was performed where applicable by removing outlier results and studies at high risk of bias.
RESULTS
Searches yielded 7195 articles; of these 15 met the inclusion criteria. A total of 320 777 patients were included. The prevalence of cirrhosis and non-alcoholic fatty liver disease (NAFLD) was 5% and 55%, respectively. Individuals with CLD had 2-fold higher mortality than those without {odds ratio [OR] 2.19 [95% confidence interval (CI) 1.39-3.45]}. Hepatitis B [OR 13.47 (95% CI 1.37-132.55)] and hepatitis C [OR 7.05 (95% CI 4.00-12.45)], but not diabetes, conferred increased cirrhosis risk. All studies examining NAFLD were judged to be at high risk of bias. We found no data on non-alcoholic steatohepatitis (NASH). Deaths from CLD, cancer and infection were greater among cirrhotic patients.
CONCLUSIONS
CLD is prevalent in dialysis patients. Hepatitis B and C confer increased risk of CLD. The impact of NAFLD and NASH cirrhosis requires further study. CLD is associated with an increased risk of mortality in this setting.
PubMed: 35371444
DOI: 10.1093/ckj/sfab230 -
Cureus Sep 2020Background Severe alcoholic hepatitis is a condition with a very high mortality rate and there is a paucity of evidence regarding efficacy and safety of most available...
Background Severe alcoholic hepatitis is a condition with a very high mortality rate and there is a paucity of evidence regarding efficacy and safety of most available therapeutic options. The present systematic review and meta-analysis aims to assess the survival benefit of granulocyte colony stimulating factor (G-CSF) in patients with severe alcoholic hepatitis. Methods Studies involving adult patients receiving G-CSF for severe alcoholic hepatitis were searched in MEDLINE, Ovid journals, MEDLINE nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model. Results The initial search identified 543 reference articles; of these 24 relevant articles were selected and reviewed. Data was extracted from four studies ( = 136) which met the inclusion criteria. In the pooled analysis, the 90-day survival in the G-CSF group was 80.03% (95% CI = 69.93-88.49) compared to 40.92% (95% CI = 29.76-52.58) in the Standard Medical Therapy (SMT) group. At 28 days, the Model for End-Stage Liver Disease (MELD) score lowered by 4.89 (95% CI = 4.13-5.64) in the G-CSF group compared to 4.00 (95% CI = 3.25-4.75) in the SMT group. Child-Turcotte-Pugh score declined by 2.26 (95% CI = 1.90-2.63) in the G-CSF group after 28 days compared to 0.91 (95% CI = 0.59-1.23) in the SMT group. At 28 days, Maddrey Discriminant Function score lowered by 39.79 (95% CI = 34.22-45.36) in the G-CSF group compared to 12.39 (95% CI = 6.90-17.88) in the SMT group. Conclusions In patients with severe alcoholic hepatitis, G-CSF therapy resulted in significantly improved 90-day survival compared to SMT. It also demonstrated significant reduction in severity indices (Child-Turcotte-Pugh, MELD, and Maddrey discriminant function) after 28 days of treatment. There certainly is a need for further studies, including development of personalized therapeutic dosing schedules, for G-CSF administration.
PubMed: 33083176
DOI: 10.7759/cureus.10474 -
BMC Public Health May 2023Alcohol related liver disease (ARLD) is one of the major chronic liver diseases worldwide. This review aimed to describe the global prevalence, incidence, and outcomes... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol related liver disease (ARLD) is one of the major chronic liver diseases worldwide. This review aimed to describe the global prevalence, incidence, and outcomes of ARLD.
METHODS
Medline, Embase, The Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to May 31, 2022. The language was restricted to English or Chinese. According to the criteria, articles describing the basic characteristics of the population were selected. Two reviewers extracted the data independently.
RESULTS
A total of 372 studies were identified: 353 were used for prevalence analysis, 7 were used for incidence analysis, and 114 were used to for outcome analysis. The prevalence of ARLD worldwide was 4.8%. The prevalence in males was 2.9%, which was higher than female (0.5%). Among the ethnic groups, the percentage was highest in Caucasians (68.9%). Alcoholic liver cirrhosis comprised the highest proportion in the disease spectrum of ARLD at 32.9%. The prevalence of ascites in ARLD population was highest (25.1%). The ARLD population who drinking for > 20 years accounted for 54.8%, and the average daily alcohol intake was 146.6 g/d. About 59.5% of ARLD patients were current or former smokers, and 18.7% were complicated with hepatitis virus infection. The incidence was 0.208/1000 person-years. The overall mortality was 23.9%, and the liver-related mortality was 21.6%.
CONCLUSION
The global prevalence of ARLD was 4.8% and was affected by sex, region, drinking years, and other factors. Therefore, removing the factors causing a high disease prevalence is an urgent requisite.
TRIAL REGISTRATION
PROSPERO Nr: CRD42021286192.
Topics: Male; Humans; Female; Prevalence; Incidence; Liver Diseases; China
PubMed: 37170239
DOI: 10.1186/s12889-023-15749-x -
International Journal of Molecular... Nov 2022Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic... (Review)
Review
Hepatocellular carcinoma (HCC) remains one of the most common malignancies and the third cause of cancer-related death worldwide, with surgery being the best prognostic tool. Among the well-known causative factors of HCC are chronic liver virus infections, chronic virus hepatitis B (HBV) and chronic hepatitis virus C (HCV), aflatoxins, tobacco consumption, and non-alcoholic liver disease (NAFLD). There is a need for the development of efficient molecular markers and alternative therapeutic targets of great significance. In this review, we describe the general characteristics of HCC and present a variety of targeted therapies that resulted in progress in HCC therapy.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Hepatitis B, Chronic; Hepacivirus; Hepatitis C, Chronic
PubMed: 36430594
DOI: 10.3390/ijms232214117 -
Molecular Nutrition & Food Research Jan 2024Akkermansia muciniphila (A. muciniphila) are Gram negative commensal bacteria, degrading mucin in the intestinal mucosa, modulating intestinal permeability and... (Review)
Review
SCOPE
Akkermansia muciniphila (A. muciniphila) are Gram negative commensal bacteria, degrading mucin in the intestinal mucosa, modulating intestinal permeability and inflammation in the digestive tract, liver, and blood. Some components can promote the relative abundance of A. muciniphila in the gut microbiota, but lower levels of A. muciniphila are more commonly found in people with obesity, diabetes, metabolic syndromes, or inflammatory digestive diseases. Over-intake of ethanol can also induce a decrease of A. muciniphila, associated with dysregulation of microbial metabolite production, impaired intestinal permeability, induction of chronic inflammation, and production of cytokines.
METHODS AND RESULTS
Using a PRISMA search strategy, a review is performed on the bacteriological characteristics of A. muciniphila, the factors capable of modulating its relative abundance in the digestive tract and its probiotic use in alcohol-related liver diseases (alcoholic hepatitis, cirrhosis, hepatocellular carcinoma, hepatic transplantation, partial hepatectomy).
CONCLUSION
Several studies have shown that supplementation with A. muciniphila can improve ethanol-related hepatic pathologies, and highlight the interest in using this bacterial species as a probiotic.
Topics: Humans; Verrucomicrobia; Liver Diseases; Inflammation; Ethanol; Akkermansia
PubMed: 38059838
DOI: 10.1002/mnfr.202300510